Effects of neonatal seizures on subsequent seizure-induced brain injury

Background: Although seizures are very common in neonates and are often the harbinger of poor neurologic outcome, there is controversy regarding the degree of brain damage induced by seizures during early development. Here, we evaluated the effect of neonatal seizures on subsequent brain injury induced by status epilepticus. Methods: Twenty-five seizures were induced by the inhalant flurothyl in neonatal rats during the first 5 days of life. Flurothyl reliably produced generalized seizures with concomitant electroencephalographic changes and a low mortality rate. During adolescence or early adulthood, animals were subjected to status epilepticus using either kainic acid or perforant path stimulation. Results: Although flurothyl-induced neonatal seizures did not cause cell death, animals that had neonatal seizures had significantly more severe brain injury after both kainic acid and perforant path stimulation than did animals without a history of neonatal seizures. Conclusions: Neonatal seizures increase the susceptibility of the developing brain to subsequent seizure-induced injury.